Most recently, we have described the G-protein coupled receptor 83 (GPR83), which is highly expressed by CD4(+)CD25(+) regulatory T cells (Tregs) to be involved in the induction of CD4(+)Foxp3(+) Tregs in the course of an ongoing immune response. Four GPR83 isoforms have been described. Here, we have shown that GPR83 isoform-4, which differs from GPR83 isoform-1 by 20 additional aminoacids in the second cytoplasmatic loop, is predominantly expressed by Tregs. Interestingly, GPR83 isoform-4 but not GPR83 isoform-1 retrovirally transduced T cells were able to interfere with inflammatory responses in vivo. Re-analysis of GPR83 transduced T cells revealed that this in vivo acquisition of suppressive activity was associated with the induction of Treg-associated molecules including Foxp3 in GPR83 isoform-4 but not GPR83 isoform-1 transduced CD4(+) T cells under inflammatory conditions. Our results suggest that the 20 additional aminoacids within GPR83 isoform-4 are involved in Treg induction during inflammatory immune responses.